Salinosporamide A (1) was discovered by Fenical et al. as a bioactive product of a marine microorganism that is widely distributed in ocean sediments. See, Fenical et al., Angew. Chem. Int. Ed., 2003, 42, 355-357. More recently, a simple stereocontrolled total synthesis of salinosporamide A was reported by Corey et al., J. Amer. Chem. Soc., 2004, 126 (20) 6230-6231.

Salinosporamide A inhibits the proteasome, an intracellular enzyme complex that destroys proteins the cell no longer needs. Without the proteasome, proteins would build up and clog cellular machinery. Fast-growing cancer cells make especially heavy use of the proteasome, so thwarting its action is a compelling drug strategy. See, Fenical et al., U.S. Patent Publication No. 2003-0157695A1 and U.S. Pat. No. 7,144,723, the disclosures of which are hereby incorporated herein by reference.